Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins
Abstract
1. Introduction
2. HPV Infection and Human Carcinogenesis
3. Keratinocytes as Mediators of Innate Immunity Against HPV Infection
4. Impact of E6/E7 on the Innate Immune Response
4.1. cGAS/STING/TBK1
4.2. RIG-I/MAVS/TBK1
4.3. TLRs
4.4. PRR-Related Transcription Factors
5. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Mechanism or Target | Cellular Model | Reference |
---|---|---|
cGAS/STING/TBK1 signaling pathway | ||
HPV18 E7 binds and antagonizes STING. | HeLa cells and mouse embryo fibroblasts stably transduced with HPV18 E6 or E7 expressing retroviruses. | Lau, L. et al., 2015 [94] |
Epigenetic silencing of cGAS and STING genes through HPV16/18 E7-mediated induction of the methyltransferase SUV39H1. | HeLa, CaSki, NIKSmcHPV18 and HEK 293 cells expressing either HPV16 or HPV18 E6 and E7. | Albertini, S. et al., 2018 [95]; Lo Cigno, I. et al., 2020 [96] |
HPV16 E7 hijacks NLRX1 to induce STING degradation via an autophagy-dependent mechanism. | HNSCC-derived cell lines ectopically expressing HPV16 E7 and a syngeneic C57/BL/6 model of HPV+ HNSCC. | Luo, X. et al., 2019 [97] |
The H3K4 lysine demethylases KDM5B and KDM5C epigenetically suppress STING mRNA expression levels. | Breast cancer cells, HPV+ head and neck and cervical carcinomas. | Wu, L. et al., 2018 [98] |
Impaired IFNβ gene transcriptional activation upon stimulation with STING agonists. | HPV16+ HNSCC-derived cell lines. | Shaikh, M.H. et al., 2019 [99] |
RIG-I/MAVS/TBK1 signaling pathway | ||
HPV16 E6 forms a ternary E6-TRIM25-USP15 complex that reduces TRIM25 protein-stability, leading to reduced ubiquitination of RIG-I and suppression of its ability to interact with MAVS. | HEK 293T and the cervical carcinoma-derived cell line C33a ectopically expressing FLAG-tagged E6 of HPV16. | Chiang, C. et al., 2018 [100] |
HPV16/18 E7 induces the transcription of SUV39H1, which promotes epigenetic silencing of RIG-I. | HeLa, CaSki, NIKSmcHPV18 and HEK 293 cells expressing either HPV16/18 E6 or E7. | Albertini, S. et al., 2018 [95]; Lo Cigno, I. et al., 2020 [96] |
TLR signaling pathway | ||
HPV16 E6/E7 induce downregulation of TLR9 expression at both mRNA and protein levels. | Human primary keratinocytes stably transduced with HPV16E6/E7 expressing retroviruses, HeLa, SiHa and CaSki. | Hasan, U.A. et al., 2007 [101] |
HPV16 suppresses TLR expression in the cervical mucosa, contributing to viral persistence. | Cervical cytobrush samples. | Daud, I.I. et al., 2011 [102]; Scott, M.E. et al., 2015 [103]; Halec, G. et al., 2018 [104] |
PRR-Related Transcription Factors | ||
HPV16 E6 binds IRF3 and impairs its transcriptional activity. | In vitro synthesized protein, and HPV16 E6-transfected cells, including primary human keratinocytes. | Ronco, L.V. et al., 1998 [93] |
HPV16 E7 binds IRF1 and impairs its DNA binding and transcriptional activity. | In vitro synthesized HPV16 E7 and HPV16E7-transfected cells. | Park, J.S. et al., 2000 [90]; Perea, S.E. et al., 2000 [91]; Um, S.J. et al., 2002 [92] |
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Lo Cigno, I.; Calati, F.; Albertini, S.; Gariglio, M. Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins. Pathogens 2020, 9, 292. https://doi.org/10.3390/pathogens9040292
Lo Cigno I, Calati F, Albertini S, Gariglio M. Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins. Pathogens. 2020; 9(4):292. https://doi.org/10.3390/pathogens9040292
Chicago/Turabian StyleLo Cigno, Irene, Federica Calati, Silvia Albertini, and Marisa Gariglio. 2020. "Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins" Pathogens 9, no. 4: 292. https://doi.org/10.3390/pathogens9040292
APA StyleLo Cigno, I., Calati, F., Albertini, S., & Gariglio, M. (2020). Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins. Pathogens, 9(4), 292. https://doi.org/10.3390/pathogens9040292